- Email: [email protected]
Acute external otitis as debut of acute myeloid leukemia - A case and review of the literature
International Journal of Pediatric Otorhinolaryngology 106 (2018) 110–112
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Acute external otitis as debut of acute myeloid leukemia - A case and review of the literature
T
Joachim Slengerik-Hansen∗, Therese Ovesen ENT-Department, Regional Hospital Holstebro, DK-7500, Holstebro, Denmark
A R T I C L E I N F O
A B S T R A C T
Keywords: Acute otitis externa Acute leukemia Necrotizing otitis externa Childhood cancer
Acute leukemia is a well known childhood cancer. The relation between leukemia and otological symptoms has long been established but is highly rare as a debut symptom of leukemia. External otitis is a common condition affecting many children, and most cases are successively treated with topical medicine. Here we present a child with acute external otitis later shown to be the debut symptom of acute myeloid leukemia, to our knowledge the first specific case described. We have reviewed the literature to find red flags for suspicion of severe disease in case of acute external otitis.
1. Introduction Leukemia is the most frequent childhood cancer accounting for approximately one third of cancer deaths in the young population [1]. Unspecific complaints are often the first symptoms which challenge early diagnostics, and as a consequence many patients are diagnosed through e.g. emergency departments [2]. Unspecific acute external otitis is a common condition often seen in the primary healthcare sector, and few are admitted to hospital as the majority of cases are cured by topical treatment for five-seven days [3]. A rare exception is necrotizing external otitis, which is characterized by poor response to initial therapy. It is often associated with systemic diseases as diabetes mellitus, and immunosuppression. The diagnosis is based on presence of granulation tissue in the external ear canal along with severe pain, serological elevated sedimentation rate, growth of Pseudomonas aeruginosa in typical cases and osteitis of the temporal bone on CT and MRI [3,4]. However, in the early stage it can be difficult to separate necrotizing external otitis from unspecific external otitis [5]. Regarding the young population, acute external otitis as well as necrotizing external otitis has been described during immunosuppressive therapy, and in relation to relapse of acute leukemia [6–8]. Acute otitis media has been found along with acute leukemia debut and relapse [9–11]. Only one case report described necrotizing external otitis as debut symptom of childhood acute lymphocytic leukemia [5]. Here we report a child presenting with severe acute external otitis as debut symptom of acute myeloid leukemia. One adult case has been described, but to our knowledge, this is the first case of acute myeloid ∗
leukemia in a child debuting with external otitis [12]. Furthermore, we discuss when to suspect severe diseases in children with external otitis. 2. Case A hitherto completely healthy 14 year old girl was admitted to the ENT department because of acute external otitis on the left side. She had a history of ear pain during one week with acute debut on a vacation in Italy with her family. There was no history of bugbite or earpicking. Prior to debut of symptoms, she and her family had been swimming in a swimmingpool, and both the patient and her father reported earpain after that. Topical treatment had no effect. She consulted a general practitioner, who referred her to a practicing otologist and a gauge embedded with ciprofloxacin/dexamethasone was placed in the ear canal along with oral penicillin treatment. The following day the situation worsened with intense pain, hearing loss, vomiting and almost no intake of food and water. On acute admission she appeared pale with affected well being. Blood pressure was 93/58, pulse 136, temperature 38.3 °C. ENT examination was normal except from swelling and soreness anteriorly of the tragus on the left side. Otomicroscopy revealed a severely inflamed and swollen left external meatus and ear canal with only a narrow view of a hyperemic tympanic membrane. On suspicion of severe external otitis or necrotizing external otitis, and septicemia, treatment with intravenous electrolyte solution, benzylpenicillin and ciprofloxacin along with continuation of topical treatment was started. Acute serology revealed severe leucopenia, neutropenia, thrombocytopenia, anemia along with increased LDH and urate. Pseudomonas
Corresponding author. E-mail address: [email protected] (J. Slengerik-Hansen).
https://doi.org/10.1016/j.ijporl.2018.01.017 Received 9 November 2017; Received in revised form 11 January 2018; Accepted 14 January 2018 Available online 02 February 2018 0165-5876/ © 2018 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 106 (2018) 110–112
J. Slengerik-Hansen, T. Ovesen
aeruginosa was grown from the external ear canal. The antimicrobial treatment was changed into broad spectrum antibiotics and the patient was transferred to the pediatric oncologic department. Here blood microscopy showed megakaryoblasts, and finally myelomonocytary leukemia was diagnosed by bone marrow biopsy. 3. Discussion External otitis is a very common disease with an incidence of approximately 1.3%, peaking between the age of seven and 12 years as well as between the age of 65–74 years [13]. Risk factors include humid warm weather, damage of the external ear canal and exposure to swimming pool water. Typical symptoms are pain, itching, decreased hearing, fullness and otorrhea [13,14]. It is well known that otologic manifestations can occur secondary to leukemia and/or the prescribed immunosuppressive therapy, and that they are caused by leukemic infiltrates, hemorrhage and infection [15,16]. But otologic diseases such as external otitis has only been described in a few cases as debut symptoms of childhood leukemia [5,9,10]. So how to suspect malignant disease and find the single needle in the haystack of acute external otitis cases among children? In other words: what are the red flags for serious underlying conditions? Clarke et al. recently published a systematic review of the clinical presentation of childhood leukemia. The study concluded that specific symptoms for instance hepatosplenomegaly alongside with more unspecific symptoms (pallor, fever, infections) appeared very commonly in the leukemic child at diagnosis. In the supplementary material only a pooled proportion of 2% showed signs of unspecific hearing impairment. In the present case the patient showed pallor, fatigue and fever, i.e. unspecific symptoms expected to be present in more than one-third of children with leukemia [1]. The patient was first prescribed topical treatment on vacation, later on consulted both a general practitioner and a private practicing otologist for treatment before admittance to an ENT department due to treatment failure. At admission, there was no suspicion of underlying malignant disease though suspicion of necrotizing external otitis was raised due to seriously affected well being. Therefore, acute blood samples were collected. Necrotizing external otitis is characterized by granulation tissue in the external ear canal, osteitis of the temporal bone, and severe pain. An important finding is lack of response to topical therapy, which can lead to delayed diagnostics of necrotizing external otitis; thus, prolonged symptoms and treatment failure should trigger a biopsy of the ear canal including imaging [4,17]. Furthermore, underlying systemic diseases such as diabetes should be highly suspected, since diabetes accounts for most of the underlying conditions in the adult and elderly population. Immunosuppression due to e.g. hematologic diseases or HIV-infections should be ruled out in especially younger patients [4,17]. Sobie et al. stated that necrotizing external otitis in children differed from necrotizing external otitis in adults, for example regarding lower incidence of underlying diabetes, and only one of 14 reviewed young patients with necrotizing external otitis had no sign of systemic disease [6]. Therefore, immunosuppressive disease should be ruled out in a child with signs of severe acute external otitis and suspicion of necrotizing external otitis. Debut of necrotizing external otitis in children appears more acutely, dominated by toxic symptoms compared to the elderly [17]. As a consequence, severe acute external otitis or necrotizing external otitis due to a severe underlying condition should be suspected early in a child not responding to relevant local treatment. The child described in the present case did not fulfill all the criteria for necrotizing external otitis, merely a case of irresponsive severe external otitis. Another condition to be considered in lack of response of relevant treatment is fungal external otitis, which demands specific antifungal therapy. It is characterized especially by itching, abscence of general symptoms, and fungal elements may be seen on otomicroscopy [3].
Fig. 1. CT cerebrum demonstrating ointment installed in the left external meatus and opaque mastoid cells. No bone destructions are seen.
4. Conclusion Here we present a case of acute myeloid leukemia heralded by acute external otitis. To our knowledge, this is the first description of acute external otitis as debut symptom in a pediatric case of acute myeloid leukemia. Clinicians should be aware of possible underlying systemic or malignant diseases in children not responding to adequate topical treatment. Furthermore, unspecific symptoms alongside with the ear symptoms are red flags for further clinical and differential-diagnostic examinations. The initial recommendation in this context is complete red and white blood count as well as measurement of blood sugar. Conflicts of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements Senior consultant Iryna Baravitskaya, Department of Radiology, Regional Hospital Holstebro is acknowledged for providing the CT scan presented in Fig. 1. Written informed consent was obtained from the parents before publication. References [1] R.T. Clarke, A. Van den Bruel, C. Bankhead, C.D. Mitchell, B. Phillips, M.J. Thompson, Clinical presentation of childhood leukaemia: a systematic review and meta-analysis, Arch. Dis. Child. 101 (10) (2016) 894–901. [2] J. Mant, V. Nanduri, Role of the 2-week urgent referral pathway in childhood cancer, Arch. Dis. Child. 97 (3) (2012) 233–235. [3] P. Schaefer, R.F. Baugh, Acute otitis externa: an update, Am. Fam. Physician 86 (11) (2012) 1055–1061. [4] P. Mahdyoun, C. Pulcini, I. Gahide, C. Raffaelli, C. Savoldelli, L. Castillo, N. Guevara, Necrotizing otitis externa: a systematic review, Otol. Neurotol. 34 (4) (2013) 620–629. [5] D.L. Pacini, T. Trevorrow, M.K. Rao, H.G. Birck, W.J. Barson, Malignant external otitis as the presentation of childhood acute lymphocytic leukemia, Pediatr. Infect. Dis. J. 15 (12) (1996) 1132–1134. [6] S. Sobie, L. Brodsky, J.F. Stanievich, Necrotizing external otitis in children: report of two cases and review of the literature, Laryngoscope 97 (5) (1987) 598–601. [7] L.J. Wollf, Necrotizing otitis externa during induction therapy for acute lymphoblastic leukemia, Pediatrics 84 (5) (1989) 882–885. [8] S.C. Sharma, A.K. Banerjee, Acute otitis externa - an unusual presentation of relapse of acute lymphoblastic leukemia, Indian J. Pathol. Microbiol. 29 (3) (1986) 215–217.
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International Journal of Pediatric Otorhinolaryngology 106 (2018) 110–112
J. Slengerik-Hansen, T. Ovesen
[13] H. Lee, J. Kim, V. Nguyen, Ear infections: otitis externa and otitis media, Prim. Care Clin. Off. Pract. 40 (3) (2013) 671–686. [14] S.L. Beers, T.J. Abramo, Otitis externa review, Pediatr. Emerg. Care 20 (4) (2004) 250–256. [15] M.M. Paparella, N.T. Berlinger, M. Oda, F. El Fiky, Otological manifestations of leukemia, Laryngoscope 83 (9) (1973) 1510–1526. [16] J.T. Fierstein, S.E. Thawley, Otolaryngologic manifestations of acute leukemia and lymphoma, South. Med. J. 71 (3) (1978) 277–280. [17] M.J. Carfrae, B.W. Kesser, Malignant otitis externa, Otolaryngol. Clin. 41 (3) (2008) 537–549.
[9] M. Feinmesser, Acute leukemia presenting as acute otitis media, AMA Arch Otolaryngol 64 (4) (1956) 346–347. [10] M.N. Kelly, S.S. Tuli, S. Usher, S.Y. Tuli, A 6-year-old with acute-onset generalized lymphadenopathy, J. Pediatr. Health Care 26 (6) (2012) 465–470. [11] N.W. Todd Jr., C.A. Bowman, Acute myelogenous leukemia presenting as atypical mastoiditis with facial paralysis, Int. J. Pediatr. Otorhinolaryngol. 7 (2) (1984) 173–177. [12] E. Andres, J.E. Kurtz, F. Maloisel, P. Dufour, Otological manifestations of acute leukaemia : report of two cases and review of literature, Clin. Lab. Haematol. 23 (1) (2001) 57–60.
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Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Acute external otitis as debut of acute myeloid leukemia - A case and review of the literature
T
Joachim Slengerik-Hansen∗, Therese Ovesen ENT-Department, Regional Hospital Holstebro, DK-7500, Holstebro, Denmark
A R T I C L E I N F O
A B S T R A C T
Keywords: Acute otitis externa Acute leukemia Necrotizing otitis externa Childhood cancer
Acute leukemia is a well known childhood cancer. The relation between leukemia and otological symptoms has long been established but is highly rare as a debut symptom of leukemia. External otitis is a common condition affecting many children, and most cases are successively treated with topical medicine. Here we present a child with acute external otitis later shown to be the debut symptom of acute myeloid leukemia, to our knowledge the first specific case described. We have reviewed the literature to find red flags for suspicion of severe disease in case of acute external otitis.
1. Introduction Leukemia is the most frequent childhood cancer accounting for approximately one third of cancer deaths in the young population [1]. Unspecific complaints are often the first symptoms which challenge early diagnostics, and as a consequence many patients are diagnosed through e.g. emergency departments [2]. Unspecific acute external otitis is a common condition often seen in the primary healthcare sector, and few are admitted to hospital as the majority of cases are cured by topical treatment for five-seven days [3]. A rare exception is necrotizing external otitis, which is characterized by poor response to initial therapy. It is often associated with systemic diseases as diabetes mellitus, and immunosuppression. The diagnosis is based on presence of granulation tissue in the external ear canal along with severe pain, serological elevated sedimentation rate, growth of Pseudomonas aeruginosa in typical cases and osteitis of the temporal bone on CT and MRI [3,4]. However, in the early stage it can be difficult to separate necrotizing external otitis from unspecific external otitis [5]. Regarding the young population, acute external otitis as well as necrotizing external otitis has been described during immunosuppressive therapy, and in relation to relapse of acute leukemia [6–8]. Acute otitis media has been found along with acute leukemia debut and relapse [9–11]. Only one case report described necrotizing external otitis as debut symptom of childhood acute lymphocytic leukemia [5]. Here we report a child presenting with severe acute external otitis as debut symptom of acute myeloid leukemia. One adult case has been described, but to our knowledge, this is the first case of acute myeloid ∗
leukemia in a child debuting with external otitis [12]. Furthermore, we discuss when to suspect severe diseases in children with external otitis. 2. Case A hitherto completely healthy 14 year old girl was admitted to the ENT department because of acute external otitis on the left side. She had a history of ear pain during one week with acute debut on a vacation in Italy with her family. There was no history of bugbite or earpicking. Prior to debut of symptoms, she and her family had been swimming in a swimmingpool, and both the patient and her father reported earpain after that. Topical treatment had no effect. She consulted a general practitioner, who referred her to a practicing otologist and a gauge embedded with ciprofloxacin/dexamethasone was placed in the ear canal along with oral penicillin treatment. The following day the situation worsened with intense pain, hearing loss, vomiting and almost no intake of food and water. On acute admission she appeared pale with affected well being. Blood pressure was 93/58, pulse 136, temperature 38.3 °C. ENT examination was normal except from swelling and soreness anteriorly of the tragus on the left side. Otomicroscopy revealed a severely inflamed and swollen left external meatus and ear canal with only a narrow view of a hyperemic tympanic membrane. On suspicion of severe external otitis or necrotizing external otitis, and septicemia, treatment with intravenous electrolyte solution, benzylpenicillin and ciprofloxacin along with continuation of topical treatment was started. Acute serology revealed severe leucopenia, neutropenia, thrombocytopenia, anemia along with increased LDH and urate. Pseudomonas
Corresponding author. E-mail address: [email protected] (J. Slengerik-Hansen).
https://doi.org/10.1016/j.ijporl.2018.01.017 Received 9 November 2017; Received in revised form 11 January 2018; Accepted 14 January 2018 Available online 02 February 2018 0165-5876/ © 2018 Elsevier B.V. All rights reserved.
International Journal of Pediatric Otorhinolaryngology 106 (2018) 110–112
J. Slengerik-Hansen, T. Ovesen
aeruginosa was grown from the external ear canal. The antimicrobial treatment was changed into broad spectrum antibiotics and the patient was transferred to the pediatric oncologic department. Here blood microscopy showed megakaryoblasts, and finally myelomonocytary leukemia was diagnosed by bone marrow biopsy. 3. Discussion External otitis is a very common disease with an incidence of approximately 1.3%, peaking between the age of seven and 12 years as well as between the age of 65–74 years [13]. Risk factors include humid warm weather, damage of the external ear canal and exposure to swimming pool water. Typical symptoms are pain, itching, decreased hearing, fullness and otorrhea [13,14]. It is well known that otologic manifestations can occur secondary to leukemia and/or the prescribed immunosuppressive therapy, and that they are caused by leukemic infiltrates, hemorrhage and infection [15,16]. But otologic diseases such as external otitis has only been described in a few cases as debut symptoms of childhood leukemia [5,9,10]. So how to suspect malignant disease and find the single needle in the haystack of acute external otitis cases among children? In other words: what are the red flags for serious underlying conditions? Clarke et al. recently published a systematic review of the clinical presentation of childhood leukemia. The study concluded that specific symptoms for instance hepatosplenomegaly alongside with more unspecific symptoms (pallor, fever, infections) appeared very commonly in the leukemic child at diagnosis. In the supplementary material only a pooled proportion of 2% showed signs of unspecific hearing impairment. In the present case the patient showed pallor, fatigue and fever, i.e. unspecific symptoms expected to be present in more than one-third of children with leukemia [1]. The patient was first prescribed topical treatment on vacation, later on consulted both a general practitioner and a private practicing otologist for treatment before admittance to an ENT department due to treatment failure. At admission, there was no suspicion of underlying malignant disease though suspicion of necrotizing external otitis was raised due to seriously affected well being. Therefore, acute blood samples were collected. Necrotizing external otitis is characterized by granulation tissue in the external ear canal, osteitis of the temporal bone, and severe pain. An important finding is lack of response to topical therapy, which can lead to delayed diagnostics of necrotizing external otitis; thus, prolonged symptoms and treatment failure should trigger a biopsy of the ear canal including imaging [4,17]. Furthermore, underlying systemic diseases such as diabetes should be highly suspected, since diabetes accounts for most of the underlying conditions in the adult and elderly population. Immunosuppression due to e.g. hematologic diseases or HIV-infections should be ruled out in especially younger patients [4,17]. Sobie et al. stated that necrotizing external otitis in children differed from necrotizing external otitis in adults, for example regarding lower incidence of underlying diabetes, and only one of 14 reviewed young patients with necrotizing external otitis had no sign of systemic disease [6]. Therefore, immunosuppressive disease should be ruled out in a child with signs of severe acute external otitis and suspicion of necrotizing external otitis. Debut of necrotizing external otitis in children appears more acutely, dominated by toxic symptoms compared to the elderly [17]. As a consequence, severe acute external otitis or necrotizing external otitis due to a severe underlying condition should be suspected early in a child not responding to relevant local treatment. The child described in the present case did not fulfill all the criteria for necrotizing external otitis, merely a case of irresponsive severe external otitis. Another condition to be considered in lack of response of relevant treatment is fungal external otitis, which demands specific antifungal therapy. It is characterized especially by itching, abscence of general symptoms, and fungal elements may be seen on otomicroscopy [3].
Fig. 1. CT cerebrum demonstrating ointment installed in the left external meatus and opaque mastoid cells. No bone destructions are seen.
4. Conclusion Here we present a case of acute myeloid leukemia heralded by acute external otitis. To our knowledge, this is the first description of acute external otitis as debut symptom in a pediatric case of acute myeloid leukemia. Clinicians should be aware of possible underlying systemic or malignant diseases in children not responding to adequate topical treatment. Furthermore, unspecific symptoms alongside with the ear symptoms are red flags for further clinical and differential-diagnostic examinations. The initial recommendation in this context is complete red and white blood count as well as measurement of blood sugar. Conflicts of interest None. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements Senior consultant Iryna Baravitskaya, Department of Radiology, Regional Hospital Holstebro is acknowledged for providing the CT scan presented in Fig. 1. Written informed consent was obtained from the parents before publication. References [1] R.T. Clarke, A. Van den Bruel, C. Bankhead, C.D. Mitchell, B. Phillips, M.J. Thompson, Clinical presentation of childhood leukaemia: a systematic review and meta-analysis, Arch. Dis. Child. 101 (10) (2016) 894–901. [2] J. Mant, V. Nanduri, Role of the 2-week urgent referral pathway in childhood cancer, Arch. Dis. Child. 97 (3) (2012) 233–235. [3] P. Schaefer, R.F. Baugh, Acute otitis externa: an update, Am. Fam. Physician 86 (11) (2012) 1055–1061. [4] P. Mahdyoun, C. Pulcini, I. Gahide, C. Raffaelli, C. Savoldelli, L. Castillo, N. Guevara, Necrotizing otitis externa: a systematic review, Otol. Neurotol. 34 (4) (2013) 620–629. [5] D.L. Pacini, T. Trevorrow, M.K. Rao, H.G. Birck, W.J. Barson, Malignant external otitis as the presentation of childhood acute lymphocytic leukemia, Pediatr. Infect. Dis. J. 15 (12) (1996) 1132–1134. [6] S. Sobie, L. Brodsky, J.F. Stanievich, Necrotizing external otitis in children: report of two cases and review of the literature, Laryngoscope 97 (5) (1987) 598–601. [7] L.J. Wollf, Necrotizing otitis externa during induction therapy for acute lymphoblastic leukemia, Pediatrics 84 (5) (1989) 882–885. [8] S.C. Sharma, A.K. Banerjee, Acute otitis externa - an unusual presentation of relapse of acute lymphoblastic leukemia, Indian J. Pathol. Microbiol. 29 (3) (1986) 215–217.
111
International Journal of Pediatric Otorhinolaryngology 106 (2018) 110–112
J. Slengerik-Hansen, T. Ovesen
[13] H. Lee, J. Kim, V. Nguyen, Ear infections: otitis externa and otitis media, Prim. Care Clin. Off. Pract. 40 (3) (2013) 671–686. [14] S.L. Beers, T.J. Abramo, Otitis externa review, Pediatr. Emerg. Care 20 (4) (2004) 250–256. [15] M.M. Paparella, N.T. Berlinger, M. Oda, F. El Fiky, Otological manifestations of leukemia, Laryngoscope 83 (9) (1973) 1510–1526. [16] J.T. Fierstein, S.E. Thawley, Otolaryngologic manifestations of acute leukemia and lymphoma, South. Med. J. 71 (3) (1978) 277–280. [17] M.J. Carfrae, B.W. Kesser, Malignant otitis externa, Otolaryngol. Clin. 41 (3) (2008) 537–549.
[9] M. Feinmesser, Acute leukemia presenting as acute otitis media, AMA Arch Otolaryngol 64 (4) (1956) 346–347. [10] M.N. Kelly, S.S. Tuli, S. Usher, S.Y. Tuli, A 6-year-old with acute-onset generalized lymphadenopathy, J. Pediatr. Health Care 26 (6) (2012) 465–470. [11] N.W. Todd Jr., C.A. Bowman, Acute myelogenous leukemia presenting as atypical mastoiditis with facial paralysis, Int. J. Pediatr. Otorhinolaryngol. 7 (2) (1984) 173–177. [12] E. Andres, J.E. Kurtz, F. Maloisel, P. Dufour, Otological manifestations of acute leukaemia : report of two cases and review of literature, Clin. Lab. Haematol. 23 (1) (2001) 57–60.
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